Non-immediate Reactions Research Articles

Immunological aspects of nonimmediate reactions to β-lactam antibiotics

β-lactam antibiotics are the agents most frequently implied in immune drug adverse reactions. These can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Mechanisms of immediate IgE-mediated reactions are widely studied and are therefore better understood. Nonimmediate reactions include a broad number of clinical entities like mild maculopapular exanthemas, the most common, and other less frequent but more severe reactions such as Stevens–Johnson syndrome, toxic epidermal necrolysis, acute exanthematic pustulosis or cytopenias. These nonimmediate reactions are mainly mediated by T cells but the precise underlying mechanisms are not well elucidated. This fact complicates the allergological evaluation of patients with this type of reaction and available tests have demonstrated poor sensitivity and specificity.

Natural killer–dendritic cell interaction in lymphocyte responses in hypersensitivity reactions to betalactams

Betalactams are the commonest cause of allergic reactions mediated by either IgE or T lymphocytes in which innate and adaptive immune systems mediate the earlier stages of immunological responses. One of the links between these systems is related to the interaction between natural killer (NK) and dendritic cells (DC). We have evaluated the role of NK cells and NK-DC interaction in the immunopathological mechanisms of nonimmediate reactions to betalactams. Patients allergic to amoxicillin (AX) (N = 17) and tolerant controls (N = 13) were included. Changes in phenotype (CD69, IFNγ, perforin, and granzyme B) in AX-stimulated NK cells, the cytotoxic activity on mature or immature DC (imDC), and the proliferation and phenotype of NK lymphocytes after culture with AX and DC were determined by flow cytometry. Amoxicillin induced activation and increases of perforin and granzyme B (P = 0.007 and P = 0.041 respectively) but not IFNγ production in NK cells from patients. In NK subpopulations, AX induced a significant enhancement of perforin and granzyme B in CD56(dim) (P = 0.005 and P = 0.002 respectively) and of IFNγ in CD56(bright) (P = 0.001). The cytotoxic phenotype was demonstrated by an increase of annexin V only in imDC (P < 0.001). Amoxicillin also induced an increased NK proliferation with different patterns, cytotoxic or proinflammatory, depending on the presence of imDC or mature DC, respectively. No differences were observed in NK cells from tolerant controls. These data could demonstrate the involvement of NK cells in the immunopathological mechanisms of nonimmediate allergic reactions to AX, showing that both the innate and adaptive immune systems are involved and crosstalk, producing amplification of the harmful effects observed in these drug reactions.

The very limited usefulness of skin testing with penicilloyl‐polylysine and the minor determinant mixture in evaluating nonimmediate reactions to penicillins

The contribution of skin testing with penicilloyl-polylysine (PPL) and the minor determinant mixture (MDM) to the diagnosis of hypersensitivity reactions to penicillins differs greatly according to the type of reaction: immediate (occurring within 1 h after the last drug administration) or nonimmediate (occurring more than 1 h after the last drug administration). To assess the contribution of skin testing with PPL and MDM to the diagnosis of nonimmediate reactions to penicillins. We evaluated 162 adults who had had 232 nonimmediate reactions to penicillins, mostly aminopenicillins, and presented positive skin and/or patch tests to one or more penicillin reagents: PPL, MDM, benzylpenicillin, ampicillin, and amoxicillin, as well as any responsible penicillins. A total of 157 subjects (96.9%) displayed patch-test and/or delayed-reading intradermal-test positivity to penicillin reagents, which indicates a cell-mediated hypersensitivity; six of them also presented immediate-reading skin-test positivities. All 157 patients with a cell-mediated hypersensitivity were positive to the responsible penicillins (parent drugs); 16 of them also displayed delayed-reading intradermal-test positivity to MDM. Five (3.1%) of the 162 patients displayed only immediate-reading skin-test positivity (four to PPL and one to amoxicillin). Overall, 158 subjects (97.5%) presented positive responses to the responsible penicillins, while only 9 (5.5%) and 17 (10.5%) were positive to PPL and MDM, respectively. The contribution of skin testing with PPL and MDM in diagnosing nonimmediate hypersensitivity reactions to penicillins, especially cell-mediated ones, is very limited. This finding could be useful at a time when PPL and MDM are not available in all countries.

Pharmakogenetik

Allergic reactions to drugs belong to the group of B-reactions, which are characterized not only by the pharmacologic profile of the drug but also by individual risk factors. Pharmacogenetic approaches facilitate identifying these risk factors. The most important example for Caucasian patients is NIDR (non-immediate drug reaction) to abacavir. Chinese patients possess risk factors for NIDR to allopurinol and anticonvulsants and the HLA locus on chromosome 6. Another potentially important area is assessing risk factors to prevent allergic reactions to antibiotics, especially with regard to the effective treatment of MRSA.

Drug provocation tests to betalactam antibiotics: experience in a paediatric setting

Background Few studies have been performed in children with suspected betalactam allergy. We aimed to assess the role of the drug provocation test (DPT) with betalactams in a paediatric setting and to study the association between allergy to betalactam antibiotics and other allergic diseases. Methods We included all the patients under 15 years old who were consecutively referred to the Immunoallergy Department, Dona Estefânia Hospital, Portugal (January 2002 to April 2008) for a compatible history of allergic reaction to betalactam. All were submitted to a DPT. Children were proposed to perform skin tests (ST) to betalactam antibiotics followed by DPT. If they decline ST, a DPT with the culprit drug was performed. Results We studied 161 children, 60% were boys, with a median age of 5 years old at the time of the DPT. Thirty-three patients (20.5%) had an immediate reaction and 33 (20.5%) a non-immediate reaction. The severity of the reported reactions was low in most cases. Skin tests to betalactams were performed in 47 children and were positive in 8. DPT was positive in only one (3.4%) of the patients skin tested and in 11 (13.4%) of those not skin tested. The severity of the DPT reaction was low. Asthma and food allergy were associated with a positive DPT in the later group . Conclusions DPT seems a safe procedure even in the absence of ST in non-severe cases. This could be a practical option in infants and pre-school children, where ST are painful and difficult to perform. Additional caution should be taken in children with asthma and food allergy.

Clinical value of negative skin tests to iodinated contrast media

Several studies have shown that skin tests are useful tools for the diagnosis of iodinated contrast medium (ICM) allergy, but the real number of false negative results is not known. To evaluate the negative predictive value of ICM skin tests. One hundred and fifty-nine patients tested in our department because of a previous ICM reaction over the last 9 years were called and asked standardized questions about ICM re-exposure. Twenty-nine patients had been re-exposed to ICM. There were 20 (69.0%) females and the median age was 55 (34-60) years. The median time interval between the reaction and skin testing was 11.9 (1.6-21.5) years. Twenty-four patients (82%) had an immediate reaction, four a non-immediate (13.8%) reaction and no data were available for one patient. Two patients had positive ICM skin tests previously and were re-exposed to a negatively skin-tested ICM and did not react. Only two patients presented a mild reaction during ICM re-injection: one immediate (generalized urticaria lasting for 3 days) and one non-immediate maculopapular reaction. The patient with urticaria was re-tested and re-challenged (negative). The other patient was unable to return for re-testing. Skin testing for ICM hypersensitivity has a negative predictive value of 96.6% (95% CI: 89.9-103.2) and none of the reactions in skin-test-negative patients were severe. Multi-centric large surveys are still needed for confirmation.

Les réintroductions médicamenteuses chez l’enfant peuvent-elles être effectuées en ambulatoire ? …oui

Diagnosis of drug allergy is based on a careful anamnesis, skin tests, and challenge tests when skin tests are not validated or are negative in patients with a suggestive clinical history. Challenge tests should only be considered after balancing the risk/benefit ratio in the patients. Theoretically, challenge tests should be performed under supervision in the hospital, due to the risk of (severe) reaction induced by the test. However, based on the experience of several authors, challenge tests may be performed at home in the children reporting non immediate and non severe reactions to useful or essential drugs for the following reasons: the diagnostic value of non-immediate reading skin tests with drugs is low, as compared with the diagnostic value of immediate-reading skin tests, and most children with non-immediate hypersensitivity to drugs are diagnosed by means of challenge tests; most of the children reporting non-immediate and non severe reactions to drugs are not allergic to the suspected drugs, and tolerate challenge tests; the onset of non-immediate reactions is dependent on the dose and length of the treatment, and most reactions induced by challenge tests performed at home in children with non-immediate drug hypersensitivity are mild to moderately severe. Thus, for these reasons and for familial and economical reasons, challenges may and should be performed at home in children reporting non immediate and non (potentially) severe reactions to drugs.

Determining the negative predictive value of provocation tests with beta‐lactams

The beta-lactam allergic work-up is mostly standardized. However, the negative predictive value of drug provocation tests is not yet well established. A historical-prospective multicentre cohort study was conducted in four centres (one in France, one in Portugal, two in Italy) to assess the negative predictive value of provocation tests with beta-lactams in patients initially tested for a suspicion of drug allergy/hypersensitivity. Patients were contacted at least 6 months after the work-up, between 2003 and 2007. A new allergic work-up was proposed to reacting patients. Among the 457 patients included, 365 (79.9%) were followed up (159 [79.1%] from France, 153 [82.7%] from Italy and 53 [74.6%] from Portugal). Only 118 (25.8%) were re-exposed to the negatively tested beta-lactam. Nine (7.6%) reported a non-immediate (occurring more than 1 h after drug administration) reaction: five urticaria, three exanthema and one undefined cutaneous reaction. None were severe. Only four accepted a re-challenge, negative in two cases and positive in the two others. The negative predictive value was 94.1% (89.8-98.3) (111 out of 118 patients). Although the negative predictive value of drug provocation tests may not be 100%, none of the false negative patients experienced a life-threatening reaction. This should reassure doctors who might hesitate to prescribe beta-lactams, even in patients with negative allergic work-ups.

Role of Amoxicillin in the Activation and Cytotoxicity of NK Against Dendritic Cells from Betalactam-Allergic Patients

RATIONALE: Interaction with pathogenic or damaged-cell molecules produces cytotoxicity and lysis of target cells by NK lymphocytes in innate immunological reactions. However, the interaction with small molecular compounds like betalactams is unknown. NK may also crosstalk with dendritic cells (DC) and induce their maturation. This study analyses the effect of amoxicillin (AX) on NK and DC from patients with allergy to this drug.METHODS: NK lymphocytes and DC were isolated from patients with non-immediate reactions to AX and healthy donors. NK were cultured in presence of several stimuli (IL12+IL15 and/or AX). Cytotoxic NK phenotype (CD69, Perforin, Granzyme-B, TNFα and IFNγ) and cytotoxicity of immature DC (imDC) and AX-matured DC (mDC) with propidium iodide (PI) and anti-annexin was determined by flow cytometry. Cell-to-cell interaction between NK and DC was analyzed by transwell co-cultures.RESULTS: Phenotypic analysis showed a significant increase of CD69, IFNγ and Granzyme in NK IL12+IL15-cultured, in both patients and controls. With AX, it showed an increase of CD69 and Granzyme in allergic subjects only. When cytotoxicity was analyzed, an increase of annexin was found in imDC cocultured with NK previously exposed to IL12+IL15, in both patients and controls, and to AX only in patients. Cytotoxicity was also significatively increased when coculturing mDC with previously IL12+IL15-activated NK in patients and controls, but AX addition produced no variation. No cytotoxicity was observed when transwell cultures were used.CONCLUSIONS: Amoxicillin activates NK from patients with non-immediate reactions to this drug, increasing cytotoxicity against DC, especially imDC. NK-DC intercellular contact is necessary for this mechanism. RATIONALE: Interaction with pathogenic or damaged-cell molecules produces cytotoxicity and lysis of target cells by NK lymphocytes in innate immunological reactions. However, the interaction with small molecular compounds like betalactams is unknown. NK may also crosstalk with dendritic cells (DC) and induce their maturation. This study analyses the effect of amoxicillin (AX) on NK and DC from patients with allergy to this drug. METHODS: NK lymphocytes and DC were isolated from patients with non-immediate reactions to AX and healthy donors. NK were cultured in presence of several stimuli (IL12+IL15 and/or AX). Cytotoxic NK phenotype (CD69, Perforin, Granzyme-B, TNFα and IFNγ) and cytotoxicity of immature DC (imDC) and AX-matured DC (mDC) with propidium iodide (PI) and anti-annexin was determined by flow cytometry. Cell-to-cell interaction between NK and DC was analyzed by transwell co-cultures. RESULTS: Phenotypic analysis showed a significant increase of CD69, IFNγ and Granzyme in NK IL12+IL15-cultured, in both patients and controls. With AX, it showed an increase of CD69 and Granzyme in allergic subjects only. When cytotoxicity was analyzed, an increase of annexin was found in imDC cocultured with NK previously exposed to IL12+IL15, in both patients and controls, and to AX only in patients. Cytotoxicity was also significatively increased when coculturing mDC with previously IL12+IL15-activated NK in patients and controls, but AX addition produced no variation. No cytotoxicity was observed when transwell cultures were used. CONCLUSIONS: Amoxicillin activates NK from patients with non-immediate reactions to this drug, increasing cytotoxicity against DC, especially imDC. NK-DC intercellular contact is necessary for this mechanism.

Update on the Management of Antibiotic Allergy

Drug allergy to antibiotics may occur in the form of immediate or non-immediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE-mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated. The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these. Severe cutaneous adverse reactions manifesting as Stevens Johnson syndrome or toxic epidermal necrolysis (TEN) may be potentially life-threatening. The management of antibiotic allergy begins with the identification of the putative antibiotic from a detailed and accurate drug history, complemented by validated in-vivo and in-vitro allergological tests. This will facilitate avoidance of the putative antibiotic through patient education, use of drug alert cards, and electronic medical records with in-built drug allergy/adverse drug reaction prescription and dispensing checks. Knowledge of the evidence for specific antibiotic cross-reactivities is also important in patient education. Apart from withdrawal of the putative antibiotic, immunomodulatory agents like high-dose intravenous immunoglobulins may have a role in TEN. Drug desensitization where the benefits outweigh the risks, and where no alternative antibiotics can be used for various reasons, may be considered in certain situations. Allergological issues pertaining to electronic drug allergy alerts, computerized physician prescriptions and decision support systems, and antibiotic de-escalation in antimicrobial stewardship programmes are also discussed.

The Time Delay Between Drug Intake and Bronchospasm for Nonsteroidal Antiinflammatory Drugs Sensitive Patients

A study was performed to assess the time between drug intake and drug induced hypersensitivity reaction for patients sensitive to nonsteroidal antiinflammatory drugs (NSAID) in clinical patient history and after oral provocation tests. Drug hypersensitivity ENDA questionnaires were filled for the patients with suspected sensitivity to NSAID. Oral provocation tests were performed with suspected NSAID according to the ENDA/EAACI recommendations. There were 76 patients with history of hypersensitivity reactions after use of NSAID enrolled in the study. Recorded were 154 hypersensitivity reactions to NSAID in the clinical history. In the clinical history median time of immediate reactions (76 cases, 81%) between drug intake and bronchospasm was 20 minutes [15-30 minutes]. Median time of nonimmediate reactions (18 cases, 19%) was 120 minutes [120-390 minutes]. There were 50 oral provocation tests performed, 14 of them (28%) were positive. Median time between drug intake and immediate reactions (8; 57% of cases) was 22.5 minutes [20-30 minutes] and median time of nonimmediate reactions (6; 43% of cases) was 167.5 minutes [125-206.25 minutes]. Time delay between drug intake and bronchospasm in the clinical history and after oral provocation test was not statistically different.

Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs

NSAIDs are the most important group of drugs involved in hypersensitivity drug reactions, and include heterogeneous compounds with very different chemical structures. These reactions can be IgE dependent (immediate reactions), T cell-mediated (non-immediate), or induced by a non-specific immunological mechanism related with the blocking of the COX-1 enzyme and the shunting to the lipooxygenase pathway (cross-intolerant reactions). Cutaneous symptoms are the most frequent, with ibuprofen, naproxen and diclofenac being common culprit drugs worldwide, although others can be involved because patterns of consumption and exposure rates vary between countries. A very important proportion of immunological reactions are immediate, with urticaria and anaphylaxis being the typical clinical manifestations. Non-immediate reactions comprise a number of heterogeneous entities ranging from mild exanthema to severe TEN or DRESS syndrome, as well as organ-specific reactions such as hepatitis or pneumonitis. Cross-intolerant reactions appear to non-chemically related drugs, and involve respiratory airways, skin or both. In vivo diagnostic tests are based on the capacity of the skin to respond to the culprit drug, but their sensitivity is in many instances rather low. The approach for in vitro testing consists of either detecting specific IgE antibodies or studying the proliferation of T lymphocytes toward the eliciting drug. No appropriate tests are yet available for the in vitro validation of cross-intolerance reactions, although techniques based on the stimulation of basophils have been proposed. Based on these findings, the diagnostic approach is often based on the controlled administration of the drug to assess tolerance. In this work we review current knowledge on hypersensitivity reactions to NSAIDs, including diagnostic approach and genetic studies.

Cross‐reactivity and tolerability of imipenem in patients with delayed‐type, cell‐mediated hypersensitivity to β‐lactams

Administration of imipenem-cilastatin to patients with IgE-mediated hypersensitivity to beta-lactams has always been considered potentially harmful. Recent studies have demonstrated the tolerability of carbapenems (imipenem-cilastatin and meropenem) in patients with IgE-mediated hypersensitivity to beta-lactams; there are no studies on this topic regarding patients with cell-mediated allergy to beta-lactams. The aim of this study is to assess cross-reactivity and tolerability of imipenem in patients with cell-mediated allergy to beta-lactams. From our database we selected 73 patients with cell-mediated allergy to beta-lactams, diagnosed by means of immediate-type skin tests, delayed reading intradermal tests, patch tests and detection of specific IgE. Patients with negative patch tests with imipenem-cilastatin underwent an intramuscular test dosing. Our patients had a total of 94 nonimmediate reactions to penicillins. All patients had positive patch tests and/or delayed reading intradermal tests for at least one of the penicillin reagent tested and negative immediate-type skin tests and specific IgE. Four patients out of 73 had a positive patch tests to at least one penicillin reagent and imipenem-cilastatin showing cross-reactivity. Sixty-four patients underwent the imipenem-cilastatin intramuscular test dosing and none of them had a clinical reaction. Our rate of cross-reactivity between imipenem-cilastatin and other beta-lactams was 5.5%. This result is different from previous findings and this may be explained by the fact that we investigated patients with cell-mediated allergy to beta-lactams. Patients with cell-mediated allergy to beta-lactams should undergo patch tests and a tolerance challenge test before treatment with imipenem-cilastatin.

Cutaneous symptoms in drug allergy: what have we learnt?

A number of studies over recent years have shown the relevance of nonimmediate immunological reactions to drugs and emphasized the need for these reactions to be studied in greater depth, including both in-vivo and in-vitro tests and provocation studies. Several clinical entities are involved, ranging from mild to severe reactions. Nonimmediate reactions have a special tropism for the skin, although other organspecific or systemic reactions may also occur. In the affected organ, the drug acts as a hapten or protohapten, originating an immunological stimulus that is followed by recruitment of T lymphocytes and other types of cells, depending on the reaction. This involves a trafficking phenomenon in which these cells use different receptors that interplay with their corresponding ligands in the tissue. In addition, a number of activation and cytotoxic markers are also expressed, which are related with disease severity. Current studies provide overwhelming evidence of the interaction between the organ involved, very often the skin, and immunocompetent cells. This is of relevance for diagnostic and therapeutic approaches.

Alergija antibakteriniams vaistams

Straipsnyje aptarti alergijos betalaktaminiams antibiotikams diagnostikos bendrieji principai. Atkreiptas dėmesys į alerginių reakcijų antibiotikams klasifikaciją (greitąsias ir negreitąsias reakcijas), padedančią pasirinkti diagnostinius tyrimus, įvertinti kryžmiškumo dažnumą. Greitosios ir negreitosios alerginės reakcijos antibiotikams skiriasi imuniniais mechanizmais, klinikiniais požymiais, diagnostika, prognoze.

Alergijos jodo turintiems radiokontrastiniams tirpalams diagnostikos, gydymo ir profilaktikos principai

Padaugėjus diagnostinių procedūrų, kurių metu reikalingi jodo turintys radiokontrastiniai tirpalai (RKT), dažniau įvyksta ir šių preparatų sukeltų nepageidaujamų reakcijų, dalį kurių lemia padidėjęs jautrumas (alergija). Visi RKT gali sukelti greitąją alerginę ir nealerginę anafilaksiją, rečiau lėtąją alerginę reakciją, kuri visada pasireiškia odoje. Tikimybė, kad greitojo tipo reakcija pasikartos kito tyrimo su RKT metu yra 21–60 proc. Taigi, jei reikia pakartotinai atlikti diagnostinę ar gydomąją procedūrą su RKT, išsiaiškinus buvusių reakcijų pobūdį, reikia pasirinkti kitą nejoninį mažo osmosiškumo tirpalą ir taikyti premedikaciją. Vis dėlto premedikacija gliukokortikoidais ir antihistamininiais vaistais neapsaugo nuo anafilaksijos, tik sumažina reakcijos sunkumą, dėl to gydytojui svarbu atpažinti alerginės reakcijos požymius ir nedelsiant juos gydyti.

Role of T cells in nonimmediate allergic drug reactions

This review presents the current knowledge of the role of T cells in drug allergy manifesting as exanthematous, pustular and bullous skin diseases, collectively referred to as nonimmediate allergic drug reactions. Both CD4+ and CD8+ T cells producing type 1 and type 2 cytokines and endowed with cytotoxic properties are involved in nonimmediate allergic drug reactions. Recent studies have confirmed that CD8+ T cells play a major role in the pathophysiology of nonimmediate allergic drug reactions, and have characterized new cytotoxic molecular pathways responsible for the severity of the bullous forms of nonimmediate allergic drug reactions. Nonimmediate allergic drug reactions are mediated by T cells and mostly affect the skin. Nonimmediate allergic drug reactions comprise several diseases ranging from the frequent and benign maculo-papular exanthema to the severe and rare toxic epidermal necrolysis. Progress in the knowledge of the pathophysiology of nonimmediate allergic drug reactions comes from a better understanding of the mechanisms of drug recognition by T cells and from a careful analysis of the phenotype and functions of CD4+ and CD8+ T cells infiltrating the skin lesions. Recent studies have confirmed that the different clinical forms of nonimmediate allergic drug reactions are associated with distinct types of T cell-mediated skin inflammation. However, CD8+ T cells appear as major effector T cells in most of the nonimmediate allergic drug reactions. Future studies to analyze the early cellular and molecular events leading to the development of the allergic skin reaction will be helpful in order to define diagnostic and therapeutic targets.

Les réactions d’hypersensibilité allergique et non allergique aux vaccins contenant des anatoxines

Most allergic (like) reactions to vaccines are reported in patients immunized with diphtheria and tetanus toxoid-containing vaccines. Local inflammatory reactions are the most frequent, but most of them are nonspecific. Diagnosis of Arthus-type reactions is based on clinical history and specific IgM/IgG anti-toxoid determination. For other local reactions (persistent nodules, sterile abscesses, etc.), diagnostic value of nonimmediate responses in skin tests varies with clinical symptoms and substances involved. Immediate responses in skin tests and specific antibody determination have good diagnostic and/or predictive value in anaphylaxis and immediate and accelerated urticaria and angioedema. Although a few generalized nonimmediate reactions may result from toxoid-specific semi-late or delayed-type hypersensitivity, most reactions are nonspecific. Withholding booster injections is advised if specific IgM/IgG levels are high. If the levels are low, sequential intramuscular injections of mono- or paucivalent vaccines are usually tolerated. However, injections of the vaccine should be performed using a “desensitization” procedure in patients reporting anaphylaxis and immediate or accelerated urticaria or angioedema.

Work up of patients with history of beta-lactam hypersensitivity

Introduction Beta-lactam antibiotics are the most frequent cause of antibiotic hypersensitivity reactions. The study of all cases of suspected beta-lactam hypersensitivity is highly important, to avoid the use of less efficient or more expensive alternatives, for fear of a reaction. Materials and methods Sixty-seven consecutive patients with suspected beta-lactam hypersensitivity reactions were studied. Skin prick tests (SPT), intradermal tests (IDT) and specific IgE determination were performed. In non-immediate reactions, epicutaneous testing was also done. If all were negative, a drug challenge was performed. Results Sixty-seven patients (54 ♀), with a mean age±SD of 36.6±19.3 years (4–78 years) were studied. The self-reported antibiotics were amoxicillin and amoxicillin/clavulanic acid in 30 (45%), penicillin in 24 (36%), cephalosporins in 11 (16%) and flucloxacillin in 2 (3%). SPT and IDT were positive in 6 patients (9%) and specific IgE in 11 (16%). Only one patient had both positive specific IgE and skin tests. Of the remaining 51 cases, 33 underwent a drug challenge with the culprit antibiotic, with a positive reaction in 2 (6%). In all positive cases and when a drug challenge with the suspected antibiotic was not indicated, a challenge with an alternative drug was done, all with negative results. Conclusions Of the 67 studied cases with history of beta-lactam hypersensitivity reactions, 18 (27%) were confirmed after testing. A combination of skin testing, specific IgE determination and drug challenge is necessary since none has sufficient sensitivity to be used alone.

Drug specific T cells in patients with a history of non-immediate hypersensitivity reactions

Drug specific T cells in patients with a history of non-immediate hypersensitivity reactions